The Changing Faces of Sequence Alignment: Fitting Alignment

Maximizing the global alignment score

Say that we wish to compare the approximately 20,000 amino acid-long NRP synthetase from Bacillus brevis with the approximately 600 amino acid-long A-domain from Streptomyces roseosporus, the bacterium that produces the powerful antibiotic Daptomycin. We hope to find a region within the longer protein sequence v that has high similarity with all of the shorter sequence w. Global alignment will not work because it tries to align all of v to all of w; local alignment will not work because it tries to align substrings of both v and w. Thus, we have a distinct alignment application called the Fitting Alignment Problem.
“Fitting” w to v requires finding a substring $v'$ of v that maximizes the global alignment score between $v'$ and w among all substrings of v. For example, the best global, local, and fitting alignments of v = CGTAGGCTTAAGGTTA and w = ATAGATA are shown in figure below (with mismatch and indel penalties equal to 1).